BIO110 Chapter 9 Lecture PDF

Chapter 9: Cell Communication BIO110: General Biology I SPRING 2024 Andrew King General Features of Cell Communication 1. Cell communication is the process of cells detecting and responding to signals in the extracellular environment 2. Signals coordinate activities in a mult...

Chapter 9: Cell Communication BIO110: General Biology I SPRING 2024 Andrew King General Features of Cell Communication 1. Cell communication is the process of cells detecting and responding to signals in the extracellular environment 2. Signals coordinate activities in a multicellular organism 3. By changing the conformation of a receptor, signals lead to a response inside the cell 4. Signals can even intentionally cause a cell to die – this is called apoptosis Figure 9.1 - Why do Cells Need Signals? Due to glucose in the environment, the yeast cell on the right has undergone a cellular response by synthesizing more glucose transporters and enzymes that are needed to metabolize glucose. Figure 9.2 - Cell Signaling Example Cell in the growing shoot tip sense light and send a signal (auxin) to cell on the nonilluminated side of the shoot. Cells located bellow the growing tip receive this signal and elongate, thereby causing a bend in the shoot. In this way, the tip grow toward the light. ©Cordelia Molloy/SPL/Science Source Figure 9.3 - Types of Cellular Signaling a)Direct intercellular signaling: b)Contact-dependent c)Autocrine signaling: Cells Signals pass through a cell junction signaling: Membrane-bound from the cytosol of one cell to adjacent signals bind to receptors on release signals that affect cells. adjacent cells. themselves and nearby target cells. d)Paracrine signaling: Cells e)Endocrine signaling: Cells release release signals that affect signals that travel long distances to nearby target cells. affect target cells. Figure 9.4 - Stages of Signal Transduction 1. Receptor activation: The binding of a 3. Cellular response: The signal transduction pathway affects the signaling molecule causes a functions and/or amounts of cellular proteins, thereby producing conformational change in a receptor a cellular response. that activates its function. 2. Signal transduction: The activated receptor stimulates a series of proteins that forms a signal transduction pathway. Figure 9.5 - Cellular Receptor Activation and Characteristics A Ligand is a signaling molecule that binds to a receptor. 1. Ligands binds noncovalently to their receptor with high specificity 2. Binding and release between receptor and ligand relatively rapid 3. Ligand binding changes receptor structure – this conformational change transmits the signal across the membrane The binding of a ligand to its receptor 4. Once a ligand is released, the receptor causes a conformational change in the reverts and receptor, resulting in receptor activation. is inactive again Figure 9.6: Cell Surface Receptors - Enzyme-Linked Receptors A signaling molecule binds and activates the catalytic domain of the receptor. Intracellular a)Structure of enzyme-linked catalytic domain b)A receptor that The receptor then receptors becomes active functions as a can catalyze the when signaling protein kinase transfer of a molecule is bound. phosphate group from ATP to an intracellular protein. Figure 9.7: Cell Surface Receptors - G-protein coupled receptors (GPCR) 2. The G protein exchanges GDP for GTP. The G 1. A signaling molecule binds protein then dissociates from the receptor and to a GPCR, causing it to β/γ dimer. separates into The activated an active a subunitsubunits and promote a bind to a G rotein. cellular responses. 3. The signaling molecule eventually dissociates from the receptor, and the α subunit hydrolyzes GTP into GDP  P. The α subunit and β/γ i dimer reassociate. the Figure 9.8: Cell Surface Receptors - Ligand-Gated Ion Channels Figure 9.9 - Intracellular Receptors 2. Estrogen receptor subunits form a dimer, bind next to specific genes, and activate their transcription. The mRNAs are then translated into proteins that affect the structure and function of the cell. 1. Estrogen diffuses across the plasma membrane, enters the nucleus, and binds to estrogen receptor subunits. The subunits undergo a conformational change. Signal Transduction and the Cellular Response 1. What produces the cellular response to signals? 2. Typically, the signaling molecule binds to cell surface receptor and the conformation change stimulates a signal transduction pathway 3. Signal transduction pathways may involve a cascade of intracellular kinases, or generation of intracellular signals called second messengers Figure 9.10: Cellular Response - Receptor Tyrosine Kinases 1. Receptor activation: Two EGF molecules bind to 2 EGF receptor subunits, causing them to dimerize and phosphorylate each other on 5. Cellular response: Myc and tyrosines. Fos stimulate the transcription of specific genes. The mRNAs are translated into proteins that cause the cell to advance through the cell cycle and divide. 2. Relay between the receptor and protein kinase cascade: Grb binds to the phosphorylated receptor and then to Sos. Sos 3. 4. stimulates Ras to release Protein kinase cascade: Activation of GDP and bind GTP. Ras activates Raf, which transcription starts a protein kinase factors: Erk enters cascade in which Raf the nucleus and phosphorylates Mek, and phosphorylates then Mek phosphorylates transcription Erk. factors, Myc and Fos. Second Messengers: Signal transduction via cAMP Signals binding to cell surface are “first messenger” Many signal transduction pathways lead to production of second messengers that relay signals inside of the cell. cAMP = Cyclic Adenosine Monophosphate Figure 9.12: GPCR Response and Second Messengers 2. The binding of the α subunit to adenylyl 1. The binding of cyclase promotes the synthesis of cAMP from epinephrine ATP. activates a GPCR. This causes the G protein to bind 3. cAMP binds to the regulatory GTP, thereby subunits of PKA, which releases promoting the  the catalytic subunits of PKA. subunit fromofβ γ dissociation the dime r. 4. The catalytic subunits of PKA use ATP to phosphorylate specific cellular proteins and thereby cause a cellular response. Figure 9.13: Protein Kinase A Activation and Function cAMP has two advantages 1. Signal amplification Binding of signal to one receptor can cause the synthesis of many cAMP molecules that activate PKA, and each PKA can phosphorylate many proteins 2. Speed In one experiment a substantial amount of cAMP was made within 20 seconds after addition of signal Figure 9.14: Signal Amplification (Protein Kinase Cascade) Figure 9.15: Speed Hormonal Signaling in Multicellular Organisms The response to a Table 9.1 Effect of given signaling Epinephrine in Humans molecule depends on Organ/ Effect which cell is Tissue responding Eye Dilates pupils Salivary Inhibits the production of saliva The variation in glands response is Skeletal Stimulates cells to break down muscle glycogen and release glucose determined by the set of proteins that Skin Constricts blood vessels; each cell makes (the stimulates sweating proteome) Lungs Relaxes airways so more oxygen is taken in Example: Epinephrine Fight-or-flight hormone Different effects throughout body Airways of the lungs relax to provide more oxygen More glycogen breakdown in skeletal muscle Heart muscle cells beat faster This explains effect of caffeine Caffeine inhibits phosphodiesterase, the enzyme that removes cAMP once the signal is gone Inhibition causes cAMP to persist, so heart beats faster even with low epinephrine A Cell’s Response to Signaling Molecules Depends on the Proteins It Makes One hormone causes different effects in different cell types Differential gene expression – all cells contain the same genome but only express particular genes Can effect cellular response in a variety of ways: 1. Receptor may not be expressed 2. Different receptors for same signal 3. Different affinities for signal 4. Signal transduction pathways different Apoptosis: Programmed Cell Death 1. Cell shrinks and forms rounder shape due to destruction of nucleus and cytoskeleton 2. Plasma membrane forms blebs – irregular extensions that break away 1. Cell beginning apoptosis 2. Condensation of 3. Multiple extensions of 4. Further blebbing nucleus and cell the plasma membrane shrinkage (1 to 4): ©Prof. Guy Whitley/Reproductive and Cardiovascular Disease Research Group at St. George's University of London Table 9.2: Abnormal Levels of Apoptosis Table 9.2 Relationship Between Certain Diseases and Abnormal Levels of Apoptosis Disease Description/Examples Diminished levels of apoptosis Cancer Cancer cells proliferate in an uncontrolled manner. In some forms of cancer, a decrease in the normal rate of apoptosis contributes to the faster proliferation rate. Examples include particular types of prostate and ovarian cancers. Elevated levels of apoptosis Viral diseases Certain viral diseases are associated with elevated levels of apoptosis. For example, infection by human immunodeficiency virus (HIV) results in an increased rate of apoptosis of helper T cells. Neurodegenerati Some neurodegenerative diseases occur because specific neurons undergo an unusually high rate of ve apoptosis. An example is Parkinson’s disease, which arises from a loss of dopaminergic neurons. diseases Figure 9.18: Apoptosis - Extrinsic Pathway 1. A signaling molecule, which is a trimer, 2. Adaptor proteins and initiator binds to 3 death receptors, causing procaspase bind to the death them to aggregate and exposing the domain, forming a death-inducing death domain. signaling complex. 3. The initiator procaspase is cleaved, and a smaller active initiator caspase is released. 4. The initiator caspase cleaves the executioner procaspase, making it active. 5. The executioner caspase cleaves cellular proteins, such as actin filaments, thereby causing the cell to shrink and eventually form blebs.